An open-label, prospective cohort, active healthcare-associated infection surveillance sequential study was conducted in four Italian intensive-care units. The aim was to determine the effect of switching from open (glass) to closed fully collapsible plastic intravenous (i.v.) infusion containers (Viaflo®) on rate and time to onset of central venous catheter-associated bloodstream infections (CVC-BSI). A total of 1173 adult patients were enrolled. The CVC-BSI rate during the open container period was significantly higher than during the closed container period (8·2 vs. 3·5 BSI/1000 CVC days, relative risk 0·43, 95% confidence interval 0·22–0·84, P=0·01). The probability of developing a CVC-BSI was assessed over time comparing open and closed i.v. infusion containers. In the closed container period, it remained fairly constant (0·8% at days 1–3 to 1·4% at days 7–9) whereas during the open container period it increased (2% at days 1–3 to 5·8% at days 7–9). Overall, the chance of acquiring a CVC-BSI significantly decreased by 61% in the closed container period (Cox proportional hazard ratio 0·39, P=0·004).